A growing body of research has attended to the experiences of transgender and gender non-conforming (TGN) youth's gender identity development. However, practical and ethical concerns have impeded our ...ability to understand the experiences of TGN youth. Thus, the aim of this study was to utilize one-on-one semi-structured interviews to explore White American TGN adults' (N = 15) retrospective accounts of their gender identity development in childhood and adolescence. Findings demonstrate considerable heterogeneity in TGN adults' retrospective accounts of their gender identity development. However, TGN adults consistently highlighted the role of social (e.g. friends, family and teachers) and contextual (e.g. online, offline, educational and geographical) factors in their gender identity journeys. This study provides new insight into the role of social and contextual factors in TGN adults' retrospective accounts of their gender identity development, demonstrating the importance of continuing to examine these factors in gender diversity research.
The interaction among topological defects can induce novel phenomena such as disclination pairs in liquid crystals and superconducting vortex lattices. Nanoscale topological vortices with swirling ...ferroelectric, magnetic, and structural antiphase relationships were found in multiferroic h-YMnO₃. Herein, we report the discovery of intriguing, but seemingly irregular configurations of a zoo of topological vortices and antivortices. These configurations can be neatly analyzed in terms of graph theory and reflect the nature of self-organized criticality in complexity phenomena. External stimuli such as chemistry-driven or electric poling can induce the condensation and eventual annihilation of topological vortex—antivortex pairs.
Integrins are a large family of heteromeric cell surface receptors composed of non-covalently bound alpha and beta subunits which interact with extracellular matrix molecules, serum constituents and ...the adhesion molecules of the immunoglobulin family. The extracellular domains of many integrins recognize the RGD (Arg-Gly-Asp) tripeptide found in several extracellular macromolecules such as fibronectin, vitronectin, fibrinogen and osteopontin. The vitronectin receptor, alpha v beta 3 integrin, is highly expressed in osteoclasts, the bone resorbing cells, and binds many of these RGD containing proteins including osteopontin, which is abundant in bone. Antibodies to alpha v beta 3, RGD peptides and RGD containing proteins such as echistatin, and kistrin were shown to inhibit bone resorption in vitro and in vivo. The identity of the alpha v beta 3 natural ligand and its mode of action in bone are so far not known. In addition to the very high levels of alpha v beta 3, mammalian osteoclasts also express alpha 2 beta 1, a collagen/laminin receptor and alpha v beta 1, another vitronectin receptor. Signaling events that follow substrate recognition by osteoclasts are not well understood. RGD containing peptides and proteins modulate Ca2+ transients in osteoclasts and phosphatidylinositol 3-kinase and pp60c-src are associated with alpha v beta 3 in these cells. alpha v and beta 3 genes were shown to be regulated by the calciotropic hormone 1,25(OH)2D3 and by a number of cytokines known to be modulators of bone metabolism. In summary, elucidation of the interactions of osteoclast integrins with components of bone matrix, may lead to further understanding of the mechanism of bone resorption.
Structural holes theory suggests a variety of possible explanations for the empirically observed relationship between structural holes and individual managerial performance. However, little has been ...done to disentangle one mechanism from another. This paper empirically tests a mediated moderation model that distinguishes between the five different theoretical mechanisms: autonomy, competition, information brokering, opportunity recognition and innovativeness. The findings suggest that of these five theoretical causal motors, innovativeness plays a key role in linking network structure and network content to performance.
Compounds containing a 1-cyanopyrrolidinyl ring were identified as potent and reversible inhibitors of cathepsins K and L. The original lead compound 1 inhibits cathepsins K and L with IC50 values of ...0.37 and 0.45 μM, respectively. Modification of compound 1 by replacement of the quinoline moiety led to the synthesis of N-(1-cyano-3-pyrrolidinyl)benzenesulfonamide (2). Compound 2 was found to be a potent inhibitor of cathepsins K and L with a K i value of 50 nM for cathepsin K. Replacement of the 1-cyanopyrrolidine of compound 2 by a 1-cyanoazetidine increased the potency of the inhibitor by 10-fold. This increase in potency is probably due to an enhanced chemical reactivity of the compound toward the thiolate of the active site of the enzyme. This is demonstrated when the assay is performed in the presence of glutathione at pH 7.0 which favors the formation of a GSH thiolate anion. Under these assay conditions, there is a loss of potency in the 1-cyanoazetidine series due to the formation of an inactive complex between the GSH thiolate and the 1-cyanoazetidine inhibitors. 1-Cyanopyrrolidinyl inhibitors exhibited time-dependent inhibition which allowed us to determine the association and dissociation rate constants with human cathepsin K. The kinetic data obtained showed that the increase of potency observed between different 1-cyanopyrrolidinyl inhibitors is due to an increase of k on values and that the association of the compound with the enzyme fits an apparent one-step mechanism. 13C NMR experiments performed with the enzyme papain showed that compound 2 forms a covalent isothiourea ester adduct with the enzyme. As predicted by the kinetic analysis, the addition of the irreversible inhibitor E64 to the enzyme−cyanopyrrolidinyl complex totally abolished the signal of the isothiourea bond as observed by 13C NMR, thereby demonstrating that the formation of the covalent bond with the active site cysteine residue is reversible. Finally, compound 2 inhibits bone resorption in an in vitro assay involving rabbit osteoclasts and bovine bone with an IC50 value of 0.7 μM. 1-Cyanopyrrolidine represents a new class of nonpeptidic compounds that inhibit cathepsin K and L activity and proteolysis of bone collagen.
This study deals with individual managerial performance, both overall and in generating innovation. While prior work has demonstrated a relationship between network structure and managerial ...performance, inadequate attention has been paid to network content. We consider several micro-social processes that might account for differences in managerial performance, taken from economic sociology and studies of managers' exploitation of their social networks and derived from work in psychology on the genesis of ideas. We compare the influence of these mechanisms on managerial performance using a sample of 106 middle managers in a European telecommunications company. Our findings suggest that, while network structure matters, access to heterogeneous knowledge is of equal importance for overall managerial performance and of greater importance for innovation performance.
Alendronate (ALN), an aminobisphosphonate used in the treatment of osteoporosis, is a potent inhibitor of bone resorption. Its molecular target is still unknown. This study examines the effects of ...ALN on the activity of osteoclast protein-tyrosine phosphatase (PTP; protein-tyrosine-phosphate phosphohydrolase, EC 3.1.3.48), called PTPε . Using osteoclast-like cells generated by coculturing mouse bone marrow cells with mouse calvaria osteoblasts, we found by molecular cloning and RNA blot hybridization that PTPε is highly expressed in osteoclastic cells. A purified fusion protein of PTPε expressed in bacteria was inhibited by ALN with an IC50 of 2 μ M. Other PTP inhibitors--orthovanadate and phenylarsine oxide (PAO)--inhibited PTPε with IC50 values of 0.3 μ M and 18 μ M, respectively. ALN and another bisphosphonate, etidronate, also inhibited the activities of other bacterially expressed PTPs such as PTPσ and CD45 (also called leukocyte common antigen). The PTP inhibitors ALN, orthovanadate, and PAO suppressed in vitro formation of multinucleated osteoclasts from osteoclast precursors and in vitro bone resorption by isolated rat osteoclasts (pit formation) with estimated IC50 values of 10 μ M, 3 μ M, and 0.05 μ M, respectively. These findings suggest that tyrosine phosphatase activity plays an important role in osteoclast formation and function and is a putative molecular target of bisphosphonate action.
The floating-zone growth of massive intermetallic single crystals is very often unsuccessful due to unfavorable solid–liquid interface geometry and insufficient mixing of the melt which depends on ...the flow in the molten zone. A tailored magnetic two-phase stirrer system with radio frequency (RF) heating has been developed which enables the control of the melt flow by a significant change of the flow field. The magnetic system was used for the crystal growth of the Heusler compound Mn3Si due to their interesting properties such an itinerant antiferromagnetic and incommensurate spin-density wave state. The grown crystals were oriented and cut to samples with the crystallographic orientations (100) and (110) normal to a plane. Measurements of the temperature dependence of magnetization and specific heat are discussed in terms of contributions of other thermodynamic phases and phase transitions.
► Single crystals of Heusler Mn3Si were grown using magnetic field controlled RF-floating-zone. ► Magnetic phase transition at about 23K was confirmed by specific heat measurements. ► Permanent magnetic moments are detected even above the ordering temperature of the majority phase. ► A probable small residual amount of impurity phase (Mn5Si2) may cause ferromagnetic contribution. ► Otherwise, it can possibly be related to a spin glass magnetic order (not to majority Mn3Si phase).
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